Elastin in the Tumor Microenvironment

Abstract

Elastic fibers are found in the extracellular matrix (ECM) of tissues requiring resilience and depend on elasticity. Elastin and its degradation products have multiple roles in the oncologic process. In many malignancies, the remodeled ECM expresses high levels of the elastin protein which may have either positive or negative effects on tumor growth. Elastin cross-linking with other ECM components and the enzymes governing this process all have effects on tumorigenesis. Elastases, and specifically neutrophil elastase, are key drivers of invasion and metastasis and therefore are important targets for inhibition. Elastin degradation leads to the generation of bioactive fragments and elastin-derived peptides that further modulate tumor growth and spread. Interestingly, elastin-like peptides (ELP) and elastin-derived peptides (EDP) may also be utilized as nano-carriers to combat tumor growth. EDPs drive tumor development in a variety of ways, and specifically targeting EDPs and their binding proteins are major objectives for ongoing and future anti-cancer therapies. Research on both the direct anti-cancer activity and the drug delivery capabilities of ELPs is another area likely to result in novel therapeutic agents in the near future.

Keywords: Elastase; Elastic fiber; Elastin; Elastin collagen cross-linking; Elastin receptor; Elastin-binding protein; Elastin-derived peptide; Elastin-like peptide; Elastoma; Elastosis; Extracellular matrix; Lysyl oxidases; Neutrophil elastase; Tumor microenvironment; Tumor-associated stroma.